Kenny Thomas P, Keen Carl L, Schmitz Harold H, Gershwin M Eric
Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis School of Medicine, 451 E. Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
Exp Biol Med (Maywood). 2007 Feb;232(2):293-300.
There has been considerable work on the relationships between nutrition and the immune response, particularly on studies that have focused on adaptive responses. There is increasing recognition of the importance of innate immunity in host protection and initiation of cytokine networks. In this study, we examined the effect of select cocoa flavanols and procyanidins on innate responses in vitro. Peripheral blood mono-nuclear cells (PBMCs), as well as purified monocytes and CD4 and CD8 T cells, were isolated from healthy volunteers and cultured in the presence of cocoa flavanol fractions that differ from another by the degree of flavanol polymerization: short-chain flavanol fraction (SCFF), monomers to pentamers; and long-chain flavanol fraction (LCFF), hexamers to decamers. Parallel investigations were also done with highly purified flavanol monomers and procyanidin dimers. The isolated cells were then challenged with lipopolysaccharide (LPS) with quantitation of activation using CD69 and CD83 expression and analysis of secreted tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, and granulocyte macrophage colony-stimulating factor (GM-CSF). The chain length of flavanol fractions had a significant effect on cytokine release from both unstimulated and LPS-stimulated PBMCs. For example, there was a striking increase of LPS-induced synthesis of IL-1beta, IL-6, IL-10, and TNF-alpha in the presence of LCFF. LCFF and SCFF, in the absence of LPS, stimulated the production of GM-CSF. In addition, LCFF and SCFF increased expression of the B cell markers CD69 and CD83. There were also unique differential responses in the mononuclear cell populations studied. We conclude that the oligomers are potent stimulators of both the innate immune system and early events in adaptive immunity.
关于营养与免疫反应之间的关系，尤其是针对适应性反应的研究，已经开展了大量工作。人们越来越认识到固有免疫在宿主保护和细胞因子网络启动中的重要性。在本研究中，我们检测了特定可可黄烷醇和原花青素对体外固有反应的影响。从健康志愿者中分离出外周血单核细胞（PBMC）以及纯化的单核细胞、CD4和CD8 T细胞，并在存在因黄烷醇聚合程度不同而相互有别的可可黄烷醇组分的情况下进行培养：短链黄烷醇组分（SCFF），单体至五聚体；以及长链黄烷醇组分（LCFF），六聚体至十聚体。还使用高度纯化的黄烷醇单体和原花青素二聚体进行了平行研究。然后用脂多糖（LPS）刺激分离出的细胞，通过CD69和CD83表达定量激活情况，并分析分泌的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6、IL-10和粒细胞巨噬细胞集落刺激因子（GM-CSF）。黄烷醇组分的链长对未刺激和LPS刺激的PBMC释放细胞因子有显著影响。例如，在存在LCFF的情况下，LPS诱导的IL-1β、IL-6、IL-10和TNF-α合成显著增加。在不存在LPS的情况下，LCFF和SCFF刺激了GM-CSF的产生。此外，LCFF和SCFF增加了B细胞标志物CD69和CD83的表达。在所研究的单核细胞群体中也存在独特的差异反应。我们得出结论，这些寡聚物是固有免疫系统和适应性免疫早期事件的有效刺激物。
